Bioorganic & Medicinal Chemistry 2010-12-01

Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands.

Xiaobo Gu, Sari Izenwasser, Dean Wade, Amy Housman, Gerard Gulasey, Jill B Rhoden, Christopher D Savoie, David L Mobley, Stacey A Lomenzo, Mark L Trudell

Index: Bioorg. Med. Chem. 18 , 8356-64, (2010)

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Abstract

A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (K(i) values <2nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).Copyright © 2010 Elsevier Ltd. All rights reserved.


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